The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is central to signaling by cytokine receptors, a superfamily of more than 30 transmembrane proteins that recognize specific cytokines, and is critical in blood formation and immune response. Canonical JAK/STAT signaling begins with the association of cytokines and their corresponding transmembrane receptors. Activated JAKs then phosphorylate latent STAT monomers, leading to dimerization, nuclear translocation, and DNA binding. In mammals, there are four JAKs (JAK1, JAK2, JAK3, TYK2) and seven STATs (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6).

JAKs are an integral component of the receptor subunit with very little release or exchange into the cytoplasm and as such are located primarily at the plasma membrane. STAT has seven conserved features: an N-terminal domain (NT), a coiled-coil domain (CC), a central DNA-binding domain (DBD), a linker region, an SH2 domain followed by a single conserved tyrosine residue, and a C-terminal transactivation domain (TAD). JAK phosphorylation of the STAT proteins then results in a spatial reorganisation of the dimer complex, and translocates to the nucleus. Once in the nucleus, STAT dimmers are stabilised by NT:NT interactions and bind cooperatively to tandem sequence elements within promoter regions to activate the transcription of specific gene subsets.

Aberrant activation of the JAK/STAT pathway has been reported in a variety of diseases, including inflammatory conditions, hematologic malignancies, and solid tumors. More recently, human myeloproliferative neoplasms are discovered to be associated with a unique acquired somatic mutation in JAK2 (JAK2 V617F), rare exon 12 JAK2 mutations, or thrombopoietin receptor mutations that constitutively activate wild-type JAK2. As a result, several drug companies have begun to develop therapeutics that inhibit the function of JAK tyrosine kinases. Currently, several JAK-targeting drugs have been used in the clinic for treating diseases including rheumatoid arthritis and myeloproliferative.

References:
[1] Kiu H, et al. Growth Factors. 2012 Apr;30(2):88-106.
[2] Quintás-Cardama A, et al. Clin Cancer Res. 2013 Apr 15;19(8):1933-40.
[3] Villarino AV, et al. J Immunol. 2015 Jan 1;194(1):21-7.
[4] Vainchenker W, et al. Oncogene. 2013 May 23;32(21):2601-13.


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Lepzacitinib

Lepzacitinib is a Janus kinase inhibitor targeting to JAK 1/3. Lepzacitinib exhibits anti-inflammatory effect and inhibits atopic dermatitis and other skin diseases[1].

  • CAS Number: 2321488-47-3
  • MF: C18H21N5O3
  • MW: 355.39
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyk2-IN-8

Tyk2-IN-8 (compound 10) is a selective TYK2 inhibitor, which binds to TYK2 catalytically active JH1 domain with an IC50 of 17 nM, used in the treatment of psoriasis[1].

  • Density: 1.46±0.1 g/cm3(Predicted)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fosifidancitinib

Fosifidancitinib is a potent and selective inhibitor of JAK kinases 1/3. Fociatinib is used in studies of allergies, asthma and autoimmune diseases[1].

  • CAS Number: 1237168-58-9
  • MF: C21H21FN5O7P
  • MW: 505.39
  • Catalog: JAK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 723.1±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 391.1±35.7 °C

H-D-Glu(Trp-OH)-OH

Golotimod (SCV-07), an immunomodulating peptide with antimicrobial activity, significantly increases the efficacy of antituberculosis therapy, stimulates thymic and splenic cell proliferation, and improves macrophage function. Golotimod (SCV-07) inhibits STAT3 signaling and modulates the duration and severity of oral mucositis in animal models that received radiation or a combination of radiation and Cisplatin. Golotimod (SCV-07) is a potential therapeutic for recurrent genital herpes simplex virus type 2 (HSV-2)[1][2][3].

  • CAS Number: 229305-39-9
  • MF: C16H19N3O5
  • MW: 333.33900
  • Catalog: Bacterial
  • Density: 1.428g/cm3
  • Boiling Point: 737.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 399.7ºC

(1E)-4-Isothiocyanato-1-(methylsulfinyl)-1-butene

Sulforaphene, isolated from radish seeds, exhibits an ED50 against velvetleaf seedlings approximately 2 x 10-4 M. Sulforaphene promotes cancer cells apoptosis and inhibits migration via inhibiting EGFR, p-ERK1/2, NF‐κB and other signals[1][2][3][4].

  • CAS Number: 592-95-0
  • MF: C6H9NOS2
  • MW: 175.272
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 362.2±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 172.8±27.9 °C

JAK3-IN-9

JAK3-IN-9 is an orally active JAK3 inhibitor with IC50 value of 1.7 nM. JAK3-IN-9 is highly selective to the JAK3 signal path. JAK3-IN-9 is lowly toxic with high oral bioavailability, shows good anti-arthritis activity. JAK3-IN-9 can be used in autoimmune disease research[1].

  • CAS Number: 1430095-30-9
  • MF: C17H23N5O4S
  • MW: 393.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CGP 52411

CGP52411 (DAPH) is a high selective, potent, orally active and ATP-competitive EGFR inhibitor with an IC50 of 0.3 μM. CGP52411 blocks the toxic influx of Ca2+ ions into neuronal cells, and dramatic inhibits and reverses the formation of β-amyloid (Aβ42) fibril aggregates associated with Alzheimer's disease[1][2].

  • CAS Number: 145915-58-8
  • MF: C20H15N3O2
  • MW: 329.35200
  • Catalog: EGFR
  • Density: 1.374 g/cm3
  • Boiling Point: N/A
  • Melting Point: 199-202℃
  • Flash Point: N/A

Tyk2-IN-9

Tyk2-IN-9 is a potent,selective and specific inhibitor of JAK kinases, inhibits Tyk2, JAK1 and JAK2 with IC50 values of 6 nM, 21nM and 6nM, respectively. Tyk2-IN-9, example 19, is extracted from patent US2017240552A1[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Benzyl-amp

IST5-002, a potent Stat5a/b inhibitor, selectively inhibits transcriptional activity of Stat5a/b (IC50s: 1.5 μM for Stat5a, 3.5 μM for Stat5b). IST5-002 inducs cell apoptotic and death of prostate cancer cells and chronic myeloid leukemia (CML) cells. IST5-002 can be used in the research of prostate cancer and chronic myeloid leukemia (CML)[1].

  • CAS Number: 13484-66-7
  • MF: C17H20N5O7P
  • MW: 437.34400
  • Catalog: Apoptosis
  • Density: 1.81g/cm3
  • Boiling Point: 798.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 436.7ºC

HX103

HX103 is an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-based fluorogenic probe. HX103 inhibits EGFR 19 del, EGFR L858R, EGFR wild type and EGFR T790M with IC50s of 1.3, 1.5, 4.0 and 977 nM, respectively. HX103 can be used for quantifying active-EGFR to predict drug sensitivity in NSCLC patients with EGFR-activating mutations[1].

  • CAS Number: 2566466-98-4
  • MF: C26H25ClFN7O5S
  • MW: 602.04
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cryptotanshinone

Cryptotanshinone is a natural compound extracted from the root of Salvia miltiorrhiza Bunge that shows antitumor activities. Cryptotanshinone inhibits STAT3 with an IC50 of 4.6 μM.

  • CAS Number: 35825-57-1
  • MF: C19H20O3
  • MW: 296.360
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 459.0±45.0 °C at 760 mmHg
  • Melting Point: 184-185ºC
  • Flash Point: 203.4±28.8 °C

Delphinidin chloride

Delphinidin chloride, an anthocyanidin, is isolated from berries and red wine. Delphinidin chloride shows endothelium-dependent vasorelaxation. Delphinidin chloride also can modulate JAK/STAT3 and MAPKinase signaling to induce apoptosis in HCT116 cells[1][2][3].

  • CAS Number: 528-53-0
  • MF: C15H11ClO7
  • MW: 338.697
  • Catalog: Apoptosis
  • Density: 1.3946 (rough estimate)
  • Boiling Point: 454.94°C (rough estimate)
  • Melting Point: >350ºC
  • Flash Point: N/A

PIM1-IN-6

PIM1-IN-6 (compound 5h) is a potent PIM-1 inhibitor, with an IC50 of 0.60 μM. PIM1-IN-6 shows the high cytotoxicity activity against HCT-116 and MCF-7 cells, with IC50 values of 1.51 and 15.2 μM, respectively[1].

  • CAS Number: 2439168-69-9
  • MF: C21H18N6O4
  • MW: 418.41
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GDC-046

GDC-046 is a potent, selective, and orally bioavailable TYK2 inhibitor with Kis of 4.8, 0.7, 0.7, and 0.4 nM for TYK2, JAK1, JAK2, and JAK3, respectively[1].

  • CAS Number: 1258292-64-6
  • MF: C16H13Cl2N3O2
  • MW: 350.199
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 518.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 267.1±30.1 °C

AG-1557

AG-1557, compound 22 (T), is a ATP competitive inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase with a pIC50 value of 8.194[1].

  • CAS Number: 189290-58-2
  • MF: C16H14IN3O2
  • MW: 407.206
  • Catalog: EGFR
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 492.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 251.9±28.7 °C

STAT3-SH2 domain inhibitor 1

STAT3-SH2 domain inhibitor 1 is a potent Src Homology 2 (SH2) Domain of STAT3 (STAT3-SH2 domain) inhibitor with a Kd value of 1.57 μM. STAT3-SH2 domain inhibitor 1 inhibits STAT3 signaling transduction and transcriptional activation. STAT3-SH2 domain inhibitor 1 induces apoptosis in gastric cancer cells. STAT3-SH2 domain inhibitor 1 can be used in research of cancer[1].

  • CAS Number: 2816059-41-1
  • MF: C28H28BF5N2O5S
  • MW: 610.40
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dacomitinib (PF-00299804)

Dacomitinib is a specific and irreversible inhibitor of the ERBB family of kinases with IC50s of 6 nM, 45.7 nM and 73.7 nM for EGFR, ERBB2, and ERBB4, respectively.

  • CAS Number: 1110813-31-4
  • MF: C24H25ClFN5O2
  • MW: 469.939
  • Catalog: EGFR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 665.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 356.4±31.5 °C

PDZ1i

PDZ1i (113B7) is a specific inhibitor of MDA-9/Syntenin activity that inhibits MDA-9/Syntenin binding to EGFRvIII; selectively binds with micromolar affinity to the PDZ1 domain of MDA-9/Syntenin, with no affinity for PDZ2 domain of MDA-9/Syntenin; reduces invasion gains in GBM cells following radiation, inhibits crucial GBM signaling involving FAK and mutant EGFR, EGFRvIII, and abrogated gains in secreted proteases, MMP-2 and MMP-9, following radiation; results in smaller, less invasive tumors and enhanced survival in an in vivo glioma model.

  • CAS Number: 2083618-79-3
  • MF: C28H26N8O
  • MW: 538.568
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zalutumumab

Zalutumumab is a high affinity, completely human IgG1 monoclonal antibody targeting EGFR. Zalutumumab binds to domain III of the EGF receptor and acts by blocking the binding of EGF and by sterically interfering with the active conformation of the receptor. Zalutumumab binds with IgG and its Fab fragment with EC50s of 7 and 19 nM, respectively. Zalutumumab can be used for the research of cancer[1][2][3].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lorpucitinib

Lorpucitinib is a Gut-Restricted JAK Inhibitor for the research of Inflammatory Bowel Disease[1].

  • CAS Number: 2230282-02-5
  • MF: C22H28N6O2
  • MW: 408.50
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pertuzumab

Pertuzumab (PBS), a humanized monoclonal antibody, is a HER2 dimerization inhibitor for the treatment of metastatic HER2-positive breast cancer.

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ubiquinone Q0

Coenzyme Q0 (CoQ0) is a potent, oral active ubiquinone compound can be derived from Antrodia cinnamomea. Coenzyme Q0 induces apoptosis and autophagy, suppresses of HER-2/AKT/mTOR signaling to potentiate the apoptosis and autophagy mechanisms. Coenzyme Q0 regulates NFκB/AP-1 activation and enhances Nrf2 stabilization in attenuation of inflammation and redox imbalance. Coenzyme Q0 has anti-angiogenic activity through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling[1][2][3].

  • CAS Number: 605-94-7
  • MF: C9H10O4
  • MW: 182.173
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 331.4±42.0 °C at 760 mmHg
  • Melting Point: 58-60 °C(lit.)
  • Flash Point: 148.6±27.9 °C

4H-Pyran-4-one,2,6-bis(4-methoxyphenyl)-

NSC81111 is a potent and orally active EGFR-TK inhibitor with an IC50 of 0.15 nM. NSC81111 has anticaner effects[1].

  • CAS Number: 1678-14-4
  • MF: C19H16O4
  • MW: 308.32800
  • Catalog: EGFR
  • Density: 1.218g/cm3
  • Boiling Point: 528.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 235.1ºC

8α-Tigloyloxyhirsutinolide 13-O-acetate

8α-Tigloyloxyhirsutinolide 13-O-acetate is a potent and orally active STAT3 inhibitor. 8α-Tigloyloxyhirsutinolide 13-O-acetate induces early oxidative stress and Pyroptosis, and late DNA damage, cell cycle arrest, Apoptosis in the TNBC cells. 8α-Tigloyloxyhirsutinolide 13-O-acetate suppresses tumor cell growth in vitro and tumor growth in vivo[1][2].

  • CAS Number: 83182-58-5
  • MF: C22H28O8
  • MW: 420.453
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 589.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 201.4±23.6 °C

CHZ868

CHZ868 is a type II JAK2 inhibitor with an IC50 of 0.17 μM in EPOR JAK2 WT Ba/F3 cell.

  • CAS Number: 1895895-38-1
  • MF: C22H19F2N5O2
  • MW: 423.415
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR/HER2/CDK9-IN-2

EGFR/HER2/CDK9-IN-2 (Compound 9) is a potent inhibitor of EGFR/HER2/CDK9 with IC50s of 145.35, 129.07, and 117.13 nM, respectively. EGFR/HER2/CDK9-IN-2 exhibits remarkable antitumor activity[1].

  • CAS Number: 1180924-34-8
  • MF: C23H20N4O5S2
  • MW: 496.56
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Khellin

Khellin, a naturally occurring furochromone, is an EGFR inhibitor with an IC50 of 0.15 µM. Khelline has anti-proliferative activity in vitro. Khellin has antispasmodic and coronary vasodilator effects[1][2].

  • CAS Number: 82-02-0
  • MF: C14H12O5
  • MW: 260.242
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 482.1±0.0 °C at 760 mmHg
  • Melting Point: 150-154ºC
  • Flash Point: 218.8±28.7 °C

Ascochlorin

Ascochlorin (Ilicicolin D), an isoprenoid antibiotic, mediates its anti-tumor effects predominantly through the suppression of STAT3 signaling cascade. Ascochlorin induces apoptosis. Anti-inflammatory activity[1][2][3].

  • CAS Number: 26166-39-2
  • MF: C23H29ClO4
  • MW: 404.92700
  • Catalog: Apoptosis
  • Density: 1.199g/cm3
  • Boiling Point: 556.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 290.6ºC

Futuximab

Futuximab is a chimeric monoclonal antibody targeting non-overlapping epitopes on EGFR. Futuximab has antineoplastic activity[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pimozide

Pimozide is a dopamine receptor antagonist, with Kis of 1.4 nM, 2.5 nM and 588 nM for dopamine D2, D3 and D1 receptors, respectively, and also has affinity at α1-adrenoceptor, with a Ki of 39 nM; Pimozide also inhibits STAT3 and STAT5.

  • CAS Number: 2062-78-4
  • MF: C28H29F2N3O
  • MW: 461.546
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 649.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 346.3±34.3 °C